Effect of acupuncture on quality of life in patients with chronic prostatitis/chronic pelvic pain syndrome: a randomized controlled trial. / é’ˆåˆºæ²»ç–—å¯¹æ ¢æ€§å‰åˆ—è ºç‚Ž/æ ¢æ€§ç›†è ”ç–¼ç—›ç»¼åˆå¾æ‚£è€ ç”Ÿæ´»è´¨é‡çš„å½±å“ï¼šéšæœºå¯¹ç §è¯•éªŒ.

OBJECTIVES: To observe the effect and safety of acupuncture on quality of life, pain, and prostate symptoms in patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). METHODS: Seventy patients with CP/CPPS were randomly divided into an acupuncture group (35 cases, 1 case was eliminated) and a sham acupuncture group (35 cases, 3 cases dropped out). The patients in the acupuncture group were treated with routine acupuncture at bilateral Zhongliao (BL 33), Huiyang (BL 35), Shenshu (BL 23) and Sanyinjiao (SP 6), while the patients in the sham acupuncture group were treated with shallow needling at non-meridian and non-acupoint points beside bilateral Zhongliao (BL 33), Huiyang (BL 35), Shenshu (BL 23) and Sanyinjiao (SP 6),without manipulation to induce arrival of qi (deqi). Both groups retained the needles for 30 min, with one session every other day, three times a week, for a total of 8 weeks (24 sessions). Before and after treatment, and at the follow-up of 24 weeks after treatment completion, the scores of MOS 36-item short-form health survey (SF-36, including 8 dimensions of physical function [PF], role physical function [RP], bodily pain [BP], general health status [GH], vitality [VT], social function [SF], role emotional [RE], and mental health [MH], which can be summarized as physical component summary [PCS] and mental component summary [MCS]), pelvic pain visual analogue scale (VAS), National Institutes of Health chronic prostatitis symptom index (NIH-CPSI), and international prostate symptom score (IPSS) were evaluated, and safety of both groups was assessed. RESULTS: After treatment and at the follow-up, the scores of each dimension and PCS, MCS scores of SF-36 in the acupuncture group were higher than those before treatment (P<0.05, P<0.01); compared before treatment, the RP, BP, and SF scores and PCS score in the sham acupuncture group were increased after treatment (P<0.05, P<0.01). After treatment, the acupuncture group had higher scores in RP, BP, GH, MH and PCS, MCS than those in the sham acupuncture group (P<0.05, P<0.01); at the follow-up, except for PF and RE dimensions, the scores in each dimension and PCS, MCS scores in the acupuncture group were higher than those in the sham acupuncture group (P<0.05, P<0.01). After treatment and at the follow-up, pelvic pain VAS, NIH-CPSI, IPSS scores in the acupuncture group were lower than those before treatment (P<0.01); in the sham acupuncture group, pelvic pain VAS, NIH-CPSI scores were lower after treatment, and NIH-CPSI score at the follow-up was lower compared with those before treatment (P<0.01). After treatment and at the follow-up, pelvic pain VAS, NIH-CPSI, IPSS scores in the acupuncture group were lower than those in the sham acupuncture group (P<0.01, P<0.05). No significant adverse reactions were observed in both groups, and the incidence rates of adverse reactions had no significant difference (P>0.05). CONCLUSIONS: Acupuncture could effectively improve the quality of life, reduce pain levels, alleviate prostate symptoms, and shows favorable long-term efficacy in patients with CP/CPPS.

Development and evaluation of short-form version of the Constitution in Chinese Medicine Questionnaire: study a new and best brief instrument of Chinese medicine for health management.

BACKGROUND: More efficient instruments for body constitution identification are needed for clinical practice. We aimed to develop the short-form version of the Constitution in Chinese Medicine Questionnaire (CCMQ) and evaluate for health management. METHODS: First, the short forms were developed through expert survey, classical test theory (CTT), and modern item response (IRT) based on the CCMQ. A combination of e-mail and manual methods was used in expert survey. Then, five indexes of CTT including criteria value-critical ratio, correlation coefficient, discrete tendency, internal consistency, and factor loading were used. And, IRT method was used through analyzing the discrimination and difficulty parameters of items. Second, the three top-ranked items of each constitution scale were selected for the simplified CCMQ, based on the three combined methods of different conditions and weights. Third, The psychometric properties such as completion time, validity (Construct, criterion, and divergent validity), and reliability (test-retest and internal consistency reliability) were evaluated. Finally, the diagnostic validity of the best short-form used receiver operating characteristic (ROC) curve. RESULTS: Three short-form editions were developed, and retained items 27, 23 and 27, which are named as WangQi nine body constitution questionnaire of Traditional Chinese Medicine (short-form) (SF-WQ9CCMQ)- A, B, and C, respectively. SF-WQ9CCMQ- A is showed the best psychometric property on Construct validity, Criterion validity, test-retest reliability and internal consistency reliability. The diagnostic validity indicated that the area under the ROC curve was 0.928 (95%CI: 0.924-0.932) for the Gentleness constitution scale, and were 0.895-0.969 and 0.911-0.981 for unbalance constitution scales using the cut-off value of the original CCMQ as 40 ("yes" standard) and 30 ("tendency" standard), respectively. CONCLUSIONS: Our study successfully developed a well short-form which has good psychometric property, and excellent diagnostic validity consistent with the original. New and simplified instrument and opportunity are provided for body constitution identification, health management and primary care implementation.

Alterations in gut microbiota and urine metabolomics in infants with yin-deficiency constitution aged 0-2 years.

Background: Based on the constitution theroy, infants are classified into balanced constitution (BC) and unbalanced constitution. Yin-deficiency constitution (YINDC) is a common type of unbalanced constitutions in Chinese infants. An infant's gut microbiota directly affects the child's health and has long-term effects on the maturation of the immune and endocrine systems throughout life. However, the gut microbiota of infants with YINDC remains unknown. Herein, we aimed to evaluate the intestinal flora profiles and urinary metabolites in infant with YINDC, find biomarkers to identify YINDC, and promote our understanding of infant constitution classification. Methods: Constitutional Medicine Questionnaires were used to assess the infants' constitution types. 47 infants with 21 cases of YINDC and 26 cases of BC were included, and a cross-sectional sampling of stool and urine was conducted. Fecal microbiota was characterized using 16S rRNA sequencing, and urinary metabolomics was profiled using UPLC-Q-TOF/MS method. YINDC markers with high accuracy were identified using receiver operating characteristic (ROC) analysis. Results: The diversity and composition of intestinal flora and urinary metabolites differed significantly between the YINDC and BC groups. A total of 13 obviously different genera and 55 altered metabolites were identified. Stool microbiome shifts were associated with urine metabolite changes. A combined marker comprising two genera may have a high potential to identify YINDC with an AUC of 0.845. Conclusions: Infants with YINDC had a unique gut microbiota and metabolomic profile resulting in a constitutional microclassification. The altered gut microbiome in YINDC may account for the higher risk of cardiovascular diseases. Metabolomic analysis of urine showed that metabolic pathways, including histidine metabolism, proximal tubule bicarbonate reclamation, arginine biosynthesis, and steroid hormone biosynthesis, were altered in infants with YINDC. Additionally, the combined bacterial biomarker had the ability to identify YINDC. Identifying YINDC in infancy and intervening at an early stage is crucial for preventing cardiovascular diseases.

Real-world data on the dose-related effect of arsenic trioxide in the relapse of acute promyelocytic leukemia.

Acute promyelocytic leukemia (APL) has become a highly curable disease with all-trans retinoic acid-based regimens. However, following the administration of arsenic trioxide (ATO), the relapse rate remains at 1-10%. It is not known whether the dosage of ATO is associated with the relapse rate in real-world settings. According to 2019 National Comprehensive Cancer Network guidelines, the recommended cumulative ATO dosage in post-remission therapy is 7.95-12 mg/kg in APL. In the current study, 112 patients with newly diagnosed APL receiving a combination of all-trans retinoic acid, anthracycline-based chemotherapy and different dosages of ATO for variable courses, were divided into the high-dose (ATO dosage, ≥12 mg/kg) and low-dose groups (ATO dosage, <12 mg/kg). Relapse risk factors were analyzed by multiple factor analysis. The relationship between relapse rate and ATO dosage in post-remission was elucidated by determining the 4-year cumulative incidence of relapse (CIR). Based on the ATO dosage in post-remission therapy, 72 (64.3%) patients were in the low-dose group and 40 (35.7%) were in the high-dose group. An increased ATO dosage was demonstrated to be an independent protective factor in terms of probability of relapse (P=0.004). With a median follow-up time of 53 months, the 4-year CIR was 16.7% in the low-dose group and 0% in the high-dose group, respectively (P=0.008). No patient relapsed when administered an ATO dosage >6 mg/kg. In conclusion, the relapse rate of APL was significantly associated with ATO dosage in post-remission therapy. An increased ATO dosage may serve as a protective factor of relapse. ATO dosage should therefore reach up to 12 mg/kg, with consideration to reduce the dosage in the future.

Mediated Drug Release from Nanovehicles by Black Phosphorus Quantum Dots for Efficient Therapy of Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is an intractable disease involving a sticky mucus layer and nanoagents with mucus-penetrating capability offer a new way to deliver drugs. However, drug release from nanovehicles requires optimization to enhance the therapeutic effects of COPD therapy. Herein, black phosphorus quantum dots (BPQDs) are combined with PEGylated chitosan nanospheres containing the antibiotic amikacin (termed PEG@CS/BPQDs-AM NPs). As a drug-delivery system, the hydrophilicity of PEG and positive charge of CS facilitate the penetration of nanovehicles through the mucus layer. The nanovehicles then adhere to the mucous membrane. Furthermore, the BPQDs degrade rapidly into nontoxic PO43- and acidic H+ , thereby promoting the dissociation of PEGylated CS nanospheres, accelerating the release of AM, decreasing the vitality of biofilms for ease of eradication. Our results reveal that drug delivery mediated by BPQDs is a feasible and desirable strategy for precision medicine and promising for the clinical therapy of COPD.

Metal-catechol-(amine) networks for surface synergistic catalytic modification: Therapeutic gas generation and biomolecule grafting.

Regarding the high requirement of cardiac and vascular implants in tissue engineering, a novel concept of surface chemistry strategy featuring multiple functions is proposed in this study, which provides glutathione peroxidase (GPx)-like catalytic activity and allows secondary reactions for grafting functional biomolecules. The suggested strategy is the fabrication of a metal-catechol-(amine) network (MCAN) containing copper ions with GPx-like activity, amine-bearing hexamethylenediamine (HD) and wet adhesive catechol dopamine (DA). With a simple one-step molecular/ion co-assembly, the developed copper-DA-HD (CuII-DA/HD) network can be used to catalyze the generation of therapeutic nitric oxide (NO) gas in a durable and dose-controllable manner. The primary amine groups in the CuII-DA/HD network facilitate the secondary immobilization of bivalirudin (BVLD) to further provide an antithrombotic activity as supplement to the functions of NO. The CuII-DA/HD + BVLD coating functionalized on cardiovascular stents successfully improved thromboresistance, anti-restenosis, and promotes re-endothelialization in vivo. With regard to the ease of operation and low cost, the synergetic modification using MCAN strategy is of great potential for developing multifunctional blood-contacting materials/devices.

Treatment of non-high-risk acute promyelocytic leukemia with realgar-indigo naturalis formula (RIF) and all-trans retinoid acid (ATRA): study protocol for a randomized controlled trial.

BACKGROUND: Acute promyelocytic leukemia (APL) is a highly curable disease when treated with all-trans retinoid acid (ATRA) and arsenic trioxide (ATO). The combination of ATO and ATRA has become the standard therapeutic protocol for induction therapy in non-high-risk APL. An oral arsenic realgar-indigo naturalis formula (RIF) has also showed high efficacy and it has a more convenient route of administration than the standard intravenous regimen. Unlike in previous trials, the arsenical agent was used simultaneously with ATRA during post-remission therapy in this trial. METHODS: This study was designed as a multicenter, randomized controlled trial. The trial has a non-inferiority design with superiority being explored if non-inferiority is identified. All patients receive ATRA-ATO during the induction therapy. After achieving hematologic complete remission (HCR), patients were randomly assigned (1:1) to receive treatment with ATRA-RIF (experimental group) or ATRA-ATO (control group) as the consolidation therapy. During the consolidation therapy, the two groups receive ATRA plus RIF or intravenous ATO 2 weeks on and 2 to ~ 4 weeks off until molecular complete remission (MCR), then ATRA and oral RIF 2 weeks on and 2 to ~ 4 weeks off giving a total of six courses. DISCUSSION: This trial aims to compare the efficacy of ATRA-ATO versus ATRA-RIF in non-high-risk patients with APL, to demonstrate that oral RIF application reduces the total hospitalization days and medical costs. The simple schedule was studied in this trial. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02899169. Registered on 14 September 2016.

Near-infrared light control of bone regeneration with biodegradable photothermal osteoimplant.

Mild heat stimulation can promote the restoration of bone defects but unfortunately, the delivery of exo-hyperthermy into human body is not efficient enough. In this study, mild heat-induced osteogenesis with high efficacy is demonstrated on an osteoimplant composed of black phosphorus nanosheets and poly(lactic-co-glycolic acid) (BPs@PLGA) with the participation of near-infrared (NIR) light irradiation. BPs@PLGA with only 0.2 wt% BPs show the highly-efficient NIR photothermal response even when being covered by a biological tissue as thick as 7 mm. In addition, this composite is completely biodegradable and the final degradation products are harmless H2O, CO2 and PO43- which can serve as necessary bone ingredient. The BPs@PLGA specimen mediated by low intensity and periodic NIR irradiation can effectively up-regulate the expressions of heat shock proteins and finally promote osteogenesis in vitro and in vivo. Boasting good biodegradability and NIR-mediated osteogenetic performances, the BPs@PLGA implant has great potential in orthopedic applications and this study provides new insights into the design and fabrication of new-style osteoimplants which can be remotely controlled.

Near-infrared light-triggered drug delivery system based on black phosphorus for in vivo bone regeneration.

A near-infrared (NIR) light-triggered drug delivery platform is produced by incorporating SrCl2 and BP nanosheets (BPs) into poly(lactic-co-glycolic acid) (PLGA) for bone regeneration. The fabricated BP-SrCl2/PLGA microspheres show efficient NIR absorption and photothermal effects due to the BPs. The NIR-triggered release behavior of Sr2+ by flawing the PLGA shells is investigated and the microspheres exhibit excellent cell viability and biodegradability. Implantation of the BP-SrCl2/PLGA microspheres into a rat femoral defect demonstrates good tissue compatibility and excellent bone regeneration capacity under NIR light irradiation. Our study indicates that local release of Sr2+ at optimal time periods controlled by NIR irradiation improves bone regeneration significantly and this NIR-triggered drug delivery system composed of BPs is suitable for therapies requiring precise control at specific time.

Biodegradable near-infrared-photoresponsive shape memory implants based on black phosphorus nanofillers.

In this paper, we propose a new shape memory polymer (SMP) composite with excellent near-infrared (NIR)-photoresponsive shape memory performance and biodegradability. The composite is fabricated by using piperazine-based polyurethane (PU) as thermo-responsive SMP incorporated with black-phosphorus (BP) sheets as NIR photothermal nanofillers. Under 808 nm light irradiation, the incorporated BP sheets with concentration of only 0.08 wt% enable rapid temperature increase over the glass temperature of PU and trigger the shape change of the composite with shape recovery rate of ∼100%. The in vitro and in vivo toxicity examinations demonstrate the good biocompatibility of the PU/BP composite, and it degrades naturally into non-toxic carbon dioxide and water from PU and non-toxic phosphate from BP. By implanting PU/BP columns into back subcutis and vagina of mice, they exhibit excellent shape memory activity to change their shape quickly under moderate 808 nm light irradiaiton. Such SMP composite enable the development of intelligent implantable devices, which can be easily controlled by the remote NIR light and degrade gradually after performing the designed functions in the body.

2D Material-Based Nanofibrous Membrane for Photothermal Cancer Therapy.

One of the clinical challenges facing photothermal cancer therapy is health risks imposed by the photothermal nanoagents in vivo. Herein, a photothermal therapy (PTT) platform composed of a 2D material-based nanofibrous membrane as the agent to deliver thermal energy to tumors under near-infrared (NIR) light irradiation is described. The photothermal membrane, which is fabricated by an electrospinning poly(l-lactic acid) (PLLA) nanofibrous membrane loaded with bismuth selenide (Bi2Se3) nanoplates, exhibits very high photothermal conversion efficiency and long-term stability. Cell experiments and hematological analyses demonstrate that the Bi2Se3/PLLA membranes have excellent biocompatibility and low toxicity. PTT experiments performed in vivo with the Bi2Se3/PLLA membrane covering the tumor and NIR irradiation produce local hyperthermia to ablate the tumor with high efficiency. Different from the traditional systematical and local injection techniques, this membrane-based PTT platform is promising in photothermal cancer therapy, especially suitable for the treatment of multiple solid tumors or skin cancers, and long-term prevention of cancer recurrence after surgery or PTT, while eliminating the health hazards of nanoagents.

Few-Layered Black Phosphorus: From Fabrication and Customization to Biomedical Applications.

As a new kind of 2D material, black phosphorus has gained increased attention in the past three years. Although few-layered black phosphorus nanosheets (BPs) degrade quickly under ambient conditions to phosphate anions, which greatly hampers their optical and electronic applications, this property also makes BPs highly biocompatible and biodegradable, and is regarded as an advantage for various biomedical applications. This Concept summarizes the state-of-art progresses of BPs, from fabrication and surface modification to biomedical applications. It is expected that BPs with such fascinating properties will encourage more scientists to engage in expanding its biomedical applications by tackling the scientific challenges involved in their development.

Improved Biocompatibility of Black Phosphorus Nanosheets by Chemical Modification.

Black phosphorus nanosheets (BPs) show great potential for various applications including biomedicine, thus their potential side effects and corresponding improvement strategy deserve investigation. Here, in vitro and in vivo biological effects of BPs with and without titanium sulfonate ligand (TiL4 ) modification are investigated. Compared to bare BPs, BPs with TiL4 modification (TiL4 @BPs) can efficiently escape from macrophages uptake, and reduce cytotoxicity and proinflammation. The corresponding mechanisms are also discussed. These findings may not only guide the applications of BPs, but also propose an efficient strategy to further improve the biocompatibility of BPs.

Cell-borne 2D nanomaterials for efficient cancer targeting and photothermal therapy.

Two of the challenges for clinical implementation of nano-therapeutic strategies are optimization of tumor targeting and clearance of the nanoagents in vivo. Herein, a cell-mediated therapy by transporting 2D Bi2Se3 nanosheets within macrophage vehicles is described. The Bi2Se3 nanosheets with excellent near-infrared photothermal performance exhibit high macrophage uptake and negligible cytotoxicity thus facilitating the fabrication of Bi2Se3-laden-macrophages. Compared with bare Bi2Se3, the Bi2Se3-laden-macrophages after intravenous injection show prolonged blood circulation and can overcome the hypoxia-associated drug delivery barrier to target the tumor efficiently and dramatically enhance the efficiency of photothermal cancer therapy. The Bi2Se3-laden-macrophages possess good biocompatibility as demonstrated by the biochemical and histological analyses and furthermore, most of the materials are excreted from the body within 25 days. Our findings reveal a desirable system for highly efficient near-infrared photothermal cancer therapy.

TiL4 -Coordinated Black Phosphorus Quantum Dots as an Efficient Contrast Agent for In Vivo Photoacoustic Imaging of Cancer.

Black phosphorus quantum dots coordinated with a sulfonic ester of the titanium ligand are prepared and exhibit enhanced stability. In vitro and in vivo photoacoustic imaging applications demonstrate that the quantum dots can efficiently accumulate inside the tumor producing tumor profiles with high spatial resolution, demonstrating their potential as an efficient agent for photoacoustic imaging.

Metabolizable Ultrathin Bi2 Se3 Nanosheets in Imaging-Guided Photothermal Therapy.

Poly(vinylpyrrolidone)-encapsulated Bi2 Se3 nanosheets with a thickness of 1.7 nm and diameter of 31.4 nm are prepared by a solution method. Possessing an extinction coefficient of 11.5 L g(-1) cm(-1) at 808 nm, the ultrathin Bi2 Se3 nanosheets boast a high photothermal conversion efficiency of 34.6% and excellent photoacoustic performance. After systemic administration, the Bi2 Se3 nanosheets with the proper size and surface properties accumulate passively in tumors enabling efficient photoacoustic imaging of the entire tumors to facilitate photothermal cancer therapy. In vivo biodistribution studies reveal that they are expelled from the body efficiently after 30 d. The ultrathin Bi2 Se3 nanosheets have large clinical potential as metabolizable near-infrared-triggered theranostic agents.

Small gold nanorods laden macrophages for enhanced tumor coverage in photothermal therapy.

One of the challenges to adopt photothermal ablation clinically is optimization of the agent delivery in vivo. Herein, a cell-mediated delivery and therapy system by employing macrophage vehicles to transport 7 nm diameter Au nanorods (sAuNRs) is described. Owing to the small size, the sAuNRs exhibit much higher macrophage uptake and negligible cytotoxicity in comparison with commonly used 14 nm diameter AuNRs to achieve healthy BSA-coated sAuNRs-laden-macrophages. By delivering BSA-coated sAuNRs to the entire tumor after intratumoral injection, the BSA-coated sAuNRs-laden-macrophages show greatly improved photothermal conversion almost everywhere in the tumor, resulting in minimized tumor recurrence rates compared to free BSA-coated sAuNRs. Our findings not only provide a desirable approach to improve the photothermal therapy efficiency by optimizing the intratumoral distribution of the agents, but also expedite clinical application of nanotechnology to cancer treatment.

Gold-nanorods-siRNA nanoplex for improved photothermal therapy by gene silencing.

Nanomaterials-mediated photothermal therapy (PTT) often suffers from the fundamental cellular defense mechanism of heat shock response which leads to therapeutic resistance of cancer cells and reduces the therapeutic efficacy. Herein, a gold nanorods (GNRs)-siRNA platform with gene silencing capability is produced to improve the PTT efficiency. After surface modification, the GNRs show the ability to deliver siRNA oligos targeting BAG3 which is an efficient gene to block the heat-shock response. The synthesized GNRs-siRNA nanoplex exhibits excellent ability in the delivery of siRNA into cancer cells with high silencing efficiency which is even better than that of commercial Lipofectamine 2000. The in vitro and in vivo studies demonstrate the ability of the GNRs-siRNA nanoplex to sensitize the cancer cells to PTT under moderate laser irradiation by down-regulating the increased BAG3 expression and enhancing apoptosis. The GNRs-siRNA mediated PTT has large potential in clinical cancer therapy due to the elimination of therapeutic resistance and enhanced photothermal therapeutic efficacy by means of gene silencing. It also suggests an efficient platform for gene delivery and controllable gene therapy.

Ultrasmall Black Phosphorus Quantum Dots: Synthesis and Use as Photothermal Agents.

Black phosphorus quantum dots (BPQDs) were synthesized using a liquid exfoliation method that combined probe sonication and bath sonication. With a lateral size of approximately 2.6 nm and a thickness of about 1.5 nm, the ultrasmall BPQDs exhibited an excellent NIR photothermal performance with a large extinction coefficient of 14.8 L g(-1) cm(-1) at 808 nm, a photothermal conversion efficiency of 28.4%, as well as good photostability. After PEG conjugation, the BPQDs showed enhanced stability in physiological medium, and there was no observable toxicity to different types of cells. NIR photoexcitation of the BPQDs in the presence of C6 and MCF7 cancer cells led to significant cell death, suggesting that the nanoparticles have large potential as photothermal agents.

[Quantitative determination of peimisin and total alkaloids in Fritillaria taipaiensis of different growing stage].

OBJECTIVE: To study the content of peimisine and total alkaloids in Fritllaria taipaiensis of different growing stage. METHODS: High performance liquid chromatography coupled with evaporative light scattering detector was employed, and peimisine was separated and quantified upon an Agilent Extend C18 (250 mm x 4.0 mm, 5 microm), using acetonitrile-water-diethylamine as the mobile phase at the flow rate of 1.0 mL min(-1); UV spectrophotometry was used for the determination of total alkaloids. RESULTS: During from two to three years period, the content of peimisine in F. taipaiensis increased with growing stage, from four to six years, it decreased with growing stage; From two to four years, the content of total alkaloids in F. taipaiensis increased with growing stage, from five to six years, it decreased with growing stage. CONCLUSION: It is suitable to harvest F. taipaienssi of four years growing stage.